Inoculation of goats with a retrovirus, caprine arthritis-encephalitis virus (CAEV), causes a progressive inflammatory arthritis that fulfills most of the diagnostic criteria for rheumatoid arthritis. The initial objectives of this proposal are to determine how the virus causes the inflammatory response in the joint and whether the immune response is causally involved. Infectious virus, viral proteins and viral genetic information will be measured in the joints of inoculated goats and compared with the severity of arthritis. Immunosuppressed goats will be used to establish the relationship between the immune response and the development of lesions. If a relationship exists, mechanisms of the immunopathogenesis will be studied. Progression of chronic arthritis will be studied with respect to mechanisms involving virus persistence and autoimmune responses. With regard to virus persistence, we will test the hypothesis that integrated provirus exists in cells undetected by the immune system and that periodic development of antigenic variants stimulate immune responses and perpetuate disease. Lesion progression by autoimmune phenomena will be approached by a search for rheumatoid factor and other evidence of polyclonal activation of immunocytes. Accomplishment of the aims of this proposal should provide a basis for comprehension of arthritis caused by persistent viral infection, and prerequisite to the goal of treatment or prevention of similar disease of people.